Treating Nightmares in Posttraumatic Stress Disorder with the a-adrenergic Agents Clonidine and Doxazosin: A Randomized-Controlled Feasibility Study (ClonDoTrial)”

Phase 1

• Conditions: Posttraumatic Stress Disorder; Therapeutic area: Psychiatry and Psychology [F] - Mental Disorders [F03]

• Registration Number: EUCTR2021-000319-21-DE
• Lead Sponsor: Charité – Universitätsmedizin Berlin

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-07-01
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 189

Inclusion Criteria

1.Diagnosis of posttraumatic stress disorder (PTSD) according to DSM 5 with a 20 item CAPS-5 total score = 26
2.At least two nightmares a week, an intensity score = 2, with a CAPS-IV B2 (frequency and intensity for the last week) score = 5
3.Men and women between 18 and 65 years of age
4.Written informed consent
5.The patient has the capacity to give consent (He/she is able to understand the nature and anticipated effects/side effects of the proposed medical intervention)
6.The patient is not breastfeeding
7.Women of child-bearing potential must have a negative urine or serum pregnancy test
8.All participants must use highly effective contraception
9. The patient received stable pharmacological medication for at least 4 weeks or at least five times the value of a elimination half-life prior to study baseline (any changes in medication dose or frequency of therapy must be answered with no)

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 189
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

1.Disturbances of cardiac impulse formation and conduction, for example sick sinus syndrome or atrioventricular block second and third degree
2.Bradycardia, with a heart rate less than 50 beats per minute
3.Current major depressive episode and a MADRS score > 34
4.The patient does have a known allergy, hypersensitivity or contraindication against clonidine, doxazosin, or other types of quinazolines
5.History of severe orthostatic hypotension
6.Benign prostatic hyperplasia and concomitant congestion of the upper urinary tract, chronic urinary tract infection or bladder stones, hypotension (for benign prostate hyperplasia only)
7.Either overflow bladder or anuria with or without progressive renal insufficiency
8.Planned cataract surgery (risk of 'Intraoperative Floppy Iris Syndrome')
9.Intake of phosphodiesterase-5-inhibitors
10.Intake of methylphenidate
11.Severe hepatic impairment (ASAT or ALAT greater than two times normal)
12.Acute or unstable medical illness
13.Known HIV- and/or active Hepatitis-B- or Hepatitis-C-infection
14.Current or past malignant illness
15.The patient does have clinically significant abnormalities in 12-lead ECG
16.The patient does have clinically significant laboratory abnormalities
17.Epilepsy
18.Dementia
19.Current substance/alcohol use disorder (= 3 months)
20.Psychotic disorder
21.Bipolar disorder
22.Current anorexia nervosa
23.Acute suicidality (any suicidal ideation of type of 5 in the C-SSRS in the past month)
24.Intake of alpha adrenergic agents (Clonidine, doxazosin, or others) within 4 weeks prior to baseline (randomization)
25.Trauma-focused psychotherapy four weeks before the trial
26.Initiation of sleep medication 4 weeks prior to baseline
27.The patient is unwilling to consent to saving, processing and propagation of pseudonymized medical data for study reasons
28.Patients, who may be dependent on the sponsor, the investigator or the trial sites
29.The patient is legally detained in an official institution
30.The patient did participated in other interventional trials during the 3 months before and at the time of this trial

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To examine whether oral clonidine (0.075-0.375 mg) or doxazosin (1-10 mg) reduces nightmares to a greater extent than placebo in patients with posttraumatic stress disorder.;Secondary Objective: Secondary objectives of the study are to examine the efficacy of oral clonidine or doxazosin in reducing other PTSD-specific symptoms, general sleep parameters and depressive symptoms in patients with posttraumatic stress disorder.;Primary end point(s): Primary efficacy endpoint: Change of Frequency and intensity of nightmares, measured with the Clinician-Administered PTSD Scale-IV (CAPS-IV) B2 score for the last week, range 0–8, from baseline until directly after last intervention (10 weeks, visit 9). A lower score indicates less frequent and/or intense nightmares.;Timepoint(s) of evaluation of this end point: Timepoint of evaluation will be done after last Intervention.